The main mission of our core is to assist NIH scientists in generating genetically engineered animal models for facilitating their scientific research. In the past 12 months, we have assisted over one dozen NIH laboratories in more than forty knockout/knockin mouse projects. In the past several years, genome engineering technology has been advancing in an extremely fast pace, and a significant portion of our efforts is devoted to keeping up with the latest technologies and efficiently applying them to animal model generation. The CRIPSR (clustered regularly interspaced short palindromic repeat) technology has remained a top priority for us in the last 4-5 years. In the past year, one exciting variant of the CRISPR-related method is the so-called base editing (BE) technology, which enables the creation of point mutations without breaking chromosomes. Our core has been collaborating with Dr. Lothar Hennighausen in the NIH Intramural Program and Dr. David Liu in the Broad Institute on applying the latest BE techniques to generate mouse models. We have successfully generated mouse lines using both cytosine base editor and adenine base editor, as well as mouse lines that harbor closely linked mutations on the same chromosome, which is difficult to achieve using the standard CRISPR/Cas method. We have also been collaborating with Dr. Hennighausen's laboratory on using the whole genome sequencing approach to address issues related to CRISPR's specificity, which is a major concern for the scientific community and general public about whether this revolutionary technology can be safely used in biomedical research and clinical applications. In addition to developing the latest technologies, we have been continuingly using the classical genetic engineering, embryonic stem cell, and assisted reproductive technologies to provide a range of services, including generating transgenic mice and chimeric mice, re-deriving mouse lines, resurrecting mouse lines using in vitro fertilization, and assessing stem cell differentiation propensities through teratoma formation assay.